The global HIV/AIDS epidemic continues to grow at an alarming rate. There are now more than 40 million people infected with HIV, most of whom will die in the next decade, and last year alone there were 5 million new infections. Most HIV transmission worldwide is through unprotected vaginal intercourse. Unprotected anal intercourse, another high risk activity, is also practiced globally by both homosexual and heterosexual individuals. Ingestion of HIV-containing breast milk by infants is a third common route of infection.
Attempts to slow the spread of HIV by behavioral measures have had little success, and no widely available biomedical intervention is available. The development of a safe and effective vaccine has proven to be extraordinarily difficult. Topical vaginal and anal microbicides are a promising alternative to vaccines because they can in principle be formulated from already-known HIV inhibitors such as reverse transcriptase inhibitors or monoclonal antibodies. However, they suffer the same fundamental problem as condoms: they have to be used each time people have sex.
A new approach is urgently needed. The present application describes an approach in which benign, commensal bacteria that can colonize mucosa of human beings are genetically engineered to secrete anti-HIV polypeptides, which then inhibit HIV infection and/or pathogenesis. The approach can also be used to genetically engineer commensal bacteria to inhibit a variety of pathogens other than HIV; e.g., other viruses, pathogenic bacteria, fungi and parasites.